Direct sub-second measurement of neuromodulator signaling during risky decision-making

项目总结 决策神经科学的许多工作都建立在多巴胺能信号起作用的假设上。 在价值表示及其更新中的关键作用，最近的工作将这种异常联系在一起 精神疾病具体特征的价值表现(例如，严重抑郁症的快感丧失)。然而， 尽管风险在评估选择方案中起着基础性的作用，以及对风险的敏感性 在精神疾病中发挥作用，包括极端的焦虑症和危害健康的行为，如物质 在另一种情况下，对风险的神经生物学的理解仍然难以捉摸。间接证据来自 药理学研究表明，5-羟色胺能和去甲肾上腺素能信号可能在 风险的表现；然而，在风险期间直接测量5-羟色胺或去甲肾上腺素信号 这种选择还有待于在人类身上进行检验。 MPI Montague团队的最新进展使追踪神经调节剂的能力达到前所未有的水平 具有高时间分辨率和化学特异性的响应。具体地说，MPI蒙塔古的团队能够 在清醒的人中直接和同时测定颞叶的多巴胺和5-羟色胺反应 检查神经调节剂释放与决策的关系所需的分辨率(~1ms) 流程。对于信号的识别和提取，记录方法使用机器学习算法 (弹性网络回归)与电化学相结合，只使用现成的硬件和软件。这个 这种“弹性网络电化学”的产物是体内神经调节剂在亚秒级波动的记录 决议。该应用程序将MPI King-Casas的决策神经科学专业知识与 MPI蒙塔古直接检测5-羟色胺、去甲肾上腺素和多巴胺能功能的研究进展 在有风险的选择期间。 为了实现这一目标，我们将记录耐药参与者的神经调节剂反应。 已经安装了用于二期监测的颅内深度电极的癫痫患者。深度电极将 由弗吉尼亚理工大学附属医疗机构Carilion Clinic(Carilion Clinic)的神经外科同事植入 派：巫师)。在录制过程中，参与者将执行i)风险引出任务(Holt&Laury类型任务)和ii)a 奖励学习任务(多臂强盗任务)，我们小组和其他人都表明可靠 当它们在标准中被监测时(即， 非手术)医院套房。深度记录将使用标准蒙太奇进行，包括多个 沿着内侧前额叶皮质的背侧-吻侧轴线接触。

PROJECT SUMMARY Much work in decision neuroscience has been predicated on the hypothesis that dopaminergic signaling plays a critical role in value representations and their updating, and recent work has linked abnormalities in such value representations to specific features of psychiatric illness (e.g., anhedonia in major depression). However, despite the fundamental role that risk plays in evaluating choice options as well as the role sensitivity to risk plays in psychiatric illness, including anxiety disorders at one extreme and health risk behaviors like substance use at another other, an understanding of the neurobiology of risk remains elusive. Indirect evidence from pharmacological studies have suggested both serotoninergic and noradrengergic signaling may play roles in representations of risk; however, direct measurement of serotonin or norepinephrine signaling during risky choice has yet to be examined in humans. Recent advances by MPI Montague’s group allow the unprecedented ability to track neuromodulator responses with high temporal resolution and chemical specificity. Specifically, MPI Montague’s team is able to directly and simultaneously measure dopamine and serotonin responses in awake humans with the temporal resolution (~ 1 ms) required to examine the relationship of neuromodulator release with decision-making processes. For signal identification and extraction, the recording method uses machine-learning algorithms (elastic net regression) combined with electrochemistry using only off-the shelf hardware and software. The product of this ‘elastic net electrochemistry’ is recordings of in vivo neuromodulator fluctuations at sub-second resolution. This application merges the decision neuroscience expertise of MPI King-Casas with these advances of MPI Montague to directly examine serotonergic, noradrenergic, and dopaminergic functioning during risky choice. To achieve this goal, we will record neuromodulator responses in participants with medication-resistant epilepsy who already have intracranial depth electrodes in place for phase-II monitoring. Depth electrodes will be implanted by our neurosurgery colleagues at Virginia Tech’s medical affiliate Carilion Clinic (Carilion Clinic PI: Witcher). During recording, participants will perform i) a risk elicitation task (Holt & Laury type task) and ii) a reward learning task (multi-arm bandit task) that have been shown by our group and others both to reliably evoke neural responses associated with risk and representations as they are monitored in a standard (i.e., non-surgical) hospital suite. Depth recordings will be made using a standard montage that includes multiple contacts along the dorsal-rostral axis of the medial prefrontal cortex.